TCR TRANSGENIC MICE IN WHICH USAGE OF TRANSGENIC ALPHA-CHAIN AND BETA-CHAIN IS HIGHLY DEPENDENT ON THE LEVEL OF SELECTING LIGAND

We have produced a TCR transgenic mouse that uses a TCR derived from a Th1 clone that is specific for residues 64 to 76 of the d allele of m urine hemoglobin presented by I-E-k. Examination of these TCR transgen ic mice on an H-2(k/k) background that expressed the nonstimulatory s allele of murine hemoglobin revealed that these mice express many endo genous TCR chains from both alpha and beta loci. We found that this tr ansgenic TCR is also very inefficient at mediating beta selection, the reby showing a direct linkage between beta selection and allelic exclu sion of TCR beta. We have also examined these mice on MHC backgrounds that have reduced levels of I-Ek and found that positive selection of cells with high levels of the transgenic TCR depends greatly on the li gand density. Decreasing the selecting ligand density is a means of re ducing the number of available selecting niches, and the data reveal t hat the 3.L2 TCR is used sparingly for positive selection under condit ions where the number of niches becomes limiting. The results, therefo re, show a way that T cells may get to the periphery with two self-res tricted TCRs: one that efficiently mediates positive selection, and an other that is inefficient at positive selection with the available nic hes.